Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [4]
It would turn out, however, that all life, bacteria included, shares the same foundation. E. coli would reveal much of that unity, and in the process it would become one of the most powerful tools biologists could use to understand life.
The transformation started with a simple question. Edward Tatum wondered if the one-gene, one-enzyme rule he discovered in mold applied to bacteria. He decided to run the mold experiment again, this time directing his X-rays at bacteria. For his experiment, Tatum chose a strain of E. coli called K-12. It had been isolated in 1922 from a California man who suffered from diphtheria, and it had been kept alive ever since at Stanford University, where it was used for microbiology classes.
Tatum’s choice was practical. Like most strains of E. coli, K-12 is harmless. E. coli is also versatile enough to build all of its own amino acids and many other molecules. For food, it needs little more than sugar, ammonia, and some trace minerals. If E. coli used a lot of enzymes to turn this food into living matter, Tatum would have plenty of targets for his X-rays. He might succeed in creating only a few mutants of the sort he was looking for, but thanks to E. coli’s luxurious growth he’d be able to see them. A single mutant could give rise to a visible colony in a day.
Tatum pelted colonies of E. coli with enough X-rays to kill 9,999 of every 10,000 bacteria. Among the few survivors he discovered mutants that could grow only if he supplied them with a particular amino acid. Helped along, the mutants could even reproduce, and their offspring were just as crippled. Tatum had gotten the same results as he had with bread mold. It looked as if behind every enzyme in E. coli lurked a gene.
It was a profound discovery, but Tatum remained cautious about its significance. It now seemed that bacteria had genes, but he could not say for sure. The best way to prove that a species had genes was to breed males and females and study their offspring. But E. coli seemed sadly celibate. “The term ‘gene’ can therefore be used in connection with bacteria only in a general sense,” Tatum wrote.
The connection became far stronger when a somber young student arrived at Tatum’s lab at Yale. Joshua Lederberg was only twenty-one years old when he began to work with Tatum, but he had a grand ambition: to find out whether bacteria had sex. As part of his military service during World War II, Lederberg had spent time in a naval hospital on Long Island, where he examined malaria parasites from marines fighting in the Pacific. He had gazed down at the single-celled protozoans, which sometimes reproduced by dividing and sometimes by taking male and female forms and mating. Perhaps bacteria had this sort of occasional sex, and no one had noticed. Others might mock the idea as a fantasy, but Lederberg decided to take what he later called “the long-shot gamble in looking for bacterial sex.”
When Lederberg heard about Tatum’s work, he realized he could look for bacterial sex with a variation on Tatum’s experiments. Tatum was amassing a collection of mutant E. coli K-12, including double mutants—bacteria that had to be fed two compounds to survive. Lederberg reasoned that if he mixed two different double mutants together, they might be able to pick up working versions of their genes through sex.
Lederberg started work at Yale in 1946. He selected a mutant strain that could make neither the amino acid methionine nor biotin, a B vitamin. The other strain he picked couldn’t make the amino acids threonine